The Unmet Need: Allogeneic HSCT is an effective treatment for aggressive leukemias and other hematological malignancies, often representing the only option for cure. However, some of its benefit, especially in the case of unrelated donor transplantation, is off-set by a high rate of transplant-related mortality (approximately 30% of recipients of unrelated donor transplantation will die of transplant-related complications) stemming largely from severe aGVHD and infection. 1-7 aGvHD occurs when reconstituting donor T cells8 become activated against recipient tissues.9 This activation can result in severe immune-mediated tissue damage to the host, with the skin, liver and GI tract being the most common targets. aGvHD-mediated damage to these vital organs can result in significant morbidity, and in death. While whole-scale T cell depletion of the allograft can successfully reduce rates of aGvHD, patients receiving T cell-depleted grafts exhibit profound defects in protective immunity, and often die of infection or relapse of their primary disease.10-12 This has created an unmet clinical need for a strategy that more effectively prevents severe aGvHD while preserving the transplant recipient's protective immune response.